tbuckley/cabot-search huggingface dataset:
Immune-interacting lymphatic endothelial subtype at capillary terminals drives lymphatic malformation
Authors: Milena Petkova, Marle Kraft, Simon Stritt, Ines Martinez-Corral, Henrik Ortsäter, Michael Vanlandewijck, Bojana Jakic, Eulàlia Baselga, Sandra D. Castillo, Mariona Graupera, Christer Betsholtz, Taija Mäkinen
Journal: The Journal of Experimental Medicine (2023)

Oncogenic mutations in PIK3CA, encoding p110α-PI3K, are a common cause of venous and lymphatic malformations. Vessel type-specific disease pathogenesis is poorly understood, hampering development of efficient therapies. Here, we reveal a new immune-interacting subtype of Ptx3-positive dermal lymphatic capillary endothelial cells (iLECs) that recruit pro-lymphangiogenic macrophages to promote progressive lymphatic overgrowth. Mouse model of Pik3caH1047R-driven vascular malformations showed that proliferation was induced in both venous and lymphatic ECs but sustained selectively in LECs of advanced lesions. Single-cell transcriptomics identified the iLEC population, residing at lymphatic capillary terminals of normal vasculature, that was expanded in Pik3caH1047R mice. Expression of pro-inflammatory genes, including monocyte/macrophage chemokine Ccl2, in Pik3caH1047R-iLECs was associated with recruitment of VEGF-C-producing macrophages. Macrophage depletion, CCL2 blockade, or anti-inflammatory COX-2 inhibition limited Pik3caH1047R-driven lymphangiogenesis. Thus, targeting the paracrine crosstalk involving iLECs and macrophages provides a new therapeutic opportunity for lymphatic malformations. Identification of iLECs further indicates that peripheral lymphatic vessels not only respond to but also actively orchestrate inflammatory processes.
Mitochondria-targeting sonosensitizer-loaded extracellular vesicles for chemo-sonodynamic therapy
Authors: Thuy Giang Nguyen Cao, Quan Truong Hoang, Eun Ji Hong, Su Jin Kang, Ji Hee Kang, Vasanthan Ravichandran, Han Chang Kang, Young Tag Ko, Won Jong Rhee, Min Suk Shim
Journal: Journal of Controlled Release (2023)
Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis
Authors: Zhuxuan Fu, Maria Mori Brooks, Sarah Irvin, Susan Jordan, Katja K H Aben, Hoda Anton-Culver, Elisa V Bandera, Matthias W Beckmann, Andrew Berchuck, Angela Brooks-Wilson, Jenny Chang-Claude, Linda S Cook, Daniel W Cramer, Kara L Cushing-Haugen, Jennifer A Doherty, Arif B Ekici, Peter A Fasching, Renée T Fortner, Simon A Gayther, Aleksandra Gentry-Maharaj, Graham G Giles, Ellen L Goode, Marc T Goodman, Holly R Harris, Alexander Hein, Rudolf Kaaks, Lambertus A Kiemeney, Martin Köbel, Joanne Kotsopoulos, Nhu D Le, Alice W Lee, Keitaro Matsuo, Valerie McGuire, John R McLaughlin, Usha Menon, Roger L Milne, Kirsten B Moysich, Celeste Leigh Pearce, Malcolm C Pike, Bo Qin, Susan J Ramus, Marjorie J Riggan, Joseph H Rothstein, Joellen M Schildkraut, Weiva Sieh, Rebecca Sutphen, Kathryn L Terry, Pamela J Thompson, Linda Titus, Anne M van Altena, Emily White, Alice S Whittemore, Anna H Wu, Wei Zheng, Argyrios Ziogas, Sarah E Taylor, Lu Tang, Thomas Songer, Nicolas Wentzensen, Penelope M Webb, Harvey A Risch, Francesmary Modugno
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. Methods LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source. Results LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes. Conclusions LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.
GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data
Authors: Shoaib Ajaib, Disha Lodha, Steven Pollock, Gemma Hemmings, Martina A Finetti, Arief Gusnanto, Aruna Chakrabarty, Azzam Ismail, Erica Wilson, Frederick S Varn, Bethany Hunter, Andrew Filby, Asa A Brockman, David McDonald, Roel G W Verhaak, Rebecca A Ihrie, Lucy F Stead
Journal: Neuro-Oncology (2023)

Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between the cellular landscape and tumor phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumor microenvironment from bulk RNA sequencing data.
Cancer-associated <i>SMARCAL1</i> loss-of-function mutations promote alternative lengthening of telomeres and tumorigenesis in telomerase-negative glioblastoma cells
Authors: Heng Liu, Cheng Xu, Bill H Diplas, Alexandrea Brown, Laura M Strickland, Haipei Yao, Jinjie Ling, Roger E McLendon, Stephen T Keir, David M Ashley, Yiping He, Matthew S Waitkus
Journal: Neuro-Oncology (2023)

Abstract Background Telomere maintenance mechanisms are required to enable the replicative immortality of malignant cells. While most cancers activate the enzyme telomerase, a subset of cancers uses telomerase-independent mechanisms termed alternative lengthening of telomeres (ALT). ALT occurs via homology-directed-repair mechanisms and is frequently associated with ATRX mutations. We previously showed that a subset of adult glioblastoma (GBM) patients with ATRX-expressing ALT-positive tumors harbored loss-of-function mutations in the SMARCAL1 gene, which encodes an annealing helicase involved in replication fork remodeling and the resolution of replication stress. However, the causative relationship between SMARCAL1 deficiency, tumorigenesis, and de novo telomere synthesis is not understood. Methods We used a patient-derived ALT-positive GBM cell line with native SMARCAL1 deficiency to investigate the role of SMARCAL1 in ALT-mediated de novo telomere synthesis, replication stress, and gliomagenesis in vivo. Results Inducible rescue of SMARCAL1 expression suppresses ALT indicators and inhibits de novo telomere synthesis in GBM and osteosarcoma cells, suggesting that SMARCAL1 deficiency plays a functional role in ALT induction in cancers that natively lack SMARCAL1 function. SMARCAL1-deficient ALT-positive cells can be serially propagated in vivo in the absence of detectable telomerase activity, demonstrating that the SMARCAL1-deficient ALT phenotype maintains telomeres in a manner that promotes tumorigenesis. Conclusions SMARCAL1 deficiency is permissive to ALT and promotes gliomagenesis. Inducible rescue of SMARCAL1 in ALT-positive cell lines permits the dynamic modulation of ALT activity, which will be valuable for future studies aimed at understanding the mechanisms of ALT and identifying novel anticancer therapeutics that target the ALT phenotype.
Use of artificial intelligence for cancer clinical trial enrollment: a systematic review and meta-analysis
Authors: Ronald Chow, Julie Midroni, Jagdeep Kaur, Gabriel Boldt, Geoffrey Liu, Lawson Eng, Fei-Fei Liu, Benjamin Haibe-Kains, Michael Lock, Srinivas Raman
Journal: JNCI Journal of the National Cancer Institute (2023)

The aim of this study is to provide a comprehensive understanding of the current landscape of artificial intelligence (AI) for cancer clinical trial enrollment and its predictive accuracy in identifying eligible patients for inclusion in such trials.
Gut-derived β-amyloid: Likely a centerpiece of the gut–brain axis contributing to Alzheimer’s pathogenesis
Authors: Jinghua Jin, Zhi Xu, Lina Zhang, Can Zhang, Xiaoduo Zhao, Yuxuan Mao, Haojian Zhang, Xingguang Liang, Juanli Wu, Ying Yang, Jing Zhang
Journal: Gut Microbes (2023)

Peripheral β-amyloid (Aβ), including those contained in the gut, may contribute to the formation of Aβ plaques in the brain, and gut microbiota appears to exert an impact on Alzheimer's disease (AD) via the gut-brain axis, although detailed mechanisms are not clearly defined. The current study focused on uncovering the potential interactions among gut-derived Aβ in aging, gut microbiota, and AD pathogenesis. To achieve this goal, the expression levels of Aβ and several key proteins involved in Aβ metabolism were initially assessed in mouse gut, with key results confirmed in human tissue. The results demonstrated that a high level of Aβ was detected throughout the gut in both mice and human, and gut Aβ42 increased with age in wild type and mutant amyloid precursor protein/presenilin 1 (APP/PS1) mice. Next, the gut microbiome of mice was characterized by 16S rRNA sequencing, and we found the gut microbiome altered significantly in aged APP/PS1 mice and fecal microbiota transplantation (FMT) of aged APP/PS1 mice increased gut BACE1 and Aβ42 levels. Intra-intestinal injection of isotope or fluorescence labeled Aβ combined with vagotomy was also performed to investigate the transmission of Aβ from gut to brain. The data showed that, in aged mice, the gut Aβ42 was transported to the brain mainly via blood rather than the vagal nerve. Furthermore, FMT of APP/PS1 mice induced neuroinflammation, a phenotype that mimics early AD pathology. Taken together, this study suggests that the gut is likely a critical source of Aβ in the brain, and gut microbiota can further upregulate gut Aβ production, thereby potentially contributing to AD pathogenesis.
Estimated Transfer of Perfluoroalkyl Substances (PFAS) from Maternal Serum to Breast Milk in Women Highly Exposed from Contaminated Drinking Water: A Study in the Ronneby Mother–Child Cohort
Authors: Annelise J. Blomberg, Erika Norén, Line S. Haug, Christian Lindh, Azemira Sabaredzovic, Daniela Pineda, Kristina Jakobsson, Christel Nielsen
Journal: Environmental Health Perspectives (2023)

Infancy perfluoroalkyl substances (PFAS) exposure from breastfeeding is partially determined by the transfer efficiencies (TEs) of PFAS from maternal serum into breast milk. However, to our knowledge there are no studies of such TEs in highly exposed populations.We estimated the TEs of PFAS from maternal serum into colostrum and breast milk in a cohort of women with a wide range of PFAS exposures.The Ronneby Mother-Child Cohort was established in 2015 after PFAS contamination was discovered in the public drinking water of Ronneby, Sweden. We measured seven PFAS in matched samples of maternal serum at delivery and colostrum and breast milk. We calculated the TE (in percentage) as the ratio of PFAS in colostrum or breast milk to serum multiplied by 100 and evaluated whether TEs varied by PFAS, lactation stage, or exposure level using a series of linear mixed-effects models with a random intercept for each woman.This study included 126 mothers. PFAS associated with firefighting foams [i.e., perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS)] were substantially elevated in the serum, colostrum, and breast milk samples of highly exposed women in the cohort and showed strong correlation. PFHxS and PFOS also contributed the largest fraction of total PFAS on average in colostrum and breast milk. Median TEs varied from 0.9% to 4.3% and were higher for perfluoroalkyl carboxylic acids, including perfluorooctanoic acid, than perfluoroalkane sulfonic acids, including PFHxS and PFOS. TEs varied by exposure level, but there was not a consistent pattern in this variation.PFAS concentrations in the colostrum and breast milk of highly exposed women were higher than the concentrations in low-exposed women, and TEs were of a similar magnitude across exposure categories. This implies that breastfeeding may be an important route of PFAS exposure for breastfeeding infants with highly exposed mothers, although the relative contribution of breastfeeding vs. prenatal transplacental transfer remains to be clarified. https://doi.org/10.1289/EHP11292.
“Double‐hit” ineffective erythropoiesis—concurrent β‐thalassemia with α‐gene triplication and myelodysplastic syndrome with <i>SF3B1</i> mutation
Authors: Po‐Han Chen, Elan Gorshein, Christopher Tormey, Alexa J. Siddon, Sudhir Perincheri
Journal: American Journal of Hematology (2023)

The authors declare no conflict of interest. The data used/analyzed in this report are available from the corresponding author on reasonable request without breaching patient confidentiality.
Molecular differences of angiogenic versus vessel co-opting colorectal cancer liver metastases at single-cell resolution
Authors: Johannes Robert Fleischer, Alexandra Maria Schmitt, Gwendolyn Haas, Xingbo Xu, Elisabeth Maria Zeisberg, Hanibal Bohnenberger, Stefan Küffer, Laure-Anne Teuwen, Philipp Johannes Karras, Tim Beißbarth, Annalen Bleckmann, Mélanie Planque, Sarah-Maria Fendt, Peter Vermeulen, Michael Ghadimi, Joanna Kalucka, Tiago De Oliveira, Lena-Christin Conradi
Journal: Molecular Cancer (2023)

Colorectal cancer liver metastases (CRCLM) are associated with a poor prognosis, reflected by a five-year survival rate of 14%. Anti-angiogenic therapy through anti-VEGF antibody administration is one of the limited therapies available. However, only a subgroup of metastases uses sprouting angiogenesis to secure their nutrients and oxygen supply, while others rely on vessel co-option (VCO). The distinct mode of vascularization is reflected by specific histopathological growth patterns (HGPs), which have proven prognostic and predictive significance. Nevertheless, their molecular mechanisms are poorly understood.We evaluated CRCLM from 225 patients regarding their HGP and clinical data. Moreover, we performed spatial (21,804 spots) and single-cell (22,419 cells) RNA sequencing analyses to explore molecular differences in detail, further validated in vitro through immunohistochemical analysis and patient-derived organoid cultures.We detected specific metabolic alterations and a signature of WNT signalling activation in metastatic cancer cells related to the VCO phenotype. Importantly, in the corresponding healthy liver of CRCLM displaying sprouting angiogenesis, we identified a predominantly expressed capillary subtype of endothelial cells, which could be further explored as a possible predictor for HGP relying on sprouting angiogenesis.These findings may prove to be novel therapeutic targets to the treatment of CRCLM, in special the ones relying on VCO.
Hypoxia signaling in cancer: Implications for therapeutic interventions
Authors: Yan Zhuang, Kua Liu, Qinyu He, Xiaosong Gu, Chunping Jiang, Junhua Wu
Journal: MedComm (2023)

Abstract Hypoxia is a persistent physiological feature of many different solid tumors and a key driver of malignancy, and in recent years, it has been recognized as an important target for cancer therapy. Hypoxia occurs in the majority of solid tumors due to a poor vascular oxygen supply that is not sufficient to meet the needs of rapidly proliferating cancer cells. A hypoxic tumor microenvironment (TME) can reduce the effectiveness of other tumor therapies, such as radiotherapy, chemotherapy, and immunotherapy. In this review, we discuss the critical role of hypoxia in tumor development, including tumor metabolism, tumor immunity, and tumor angiogenesis. The treatment methods for hypoxic TME are summarized, including hypoxia‐targeted therapy and improving oxygenation by alleviating tumor hypoxia itself. Hyperoxia therapy can be used to improve tissue oxygen partial pressure and relieve tumor hypoxia. We focus on the underlying mechanisms of hyperoxia and their impact on current cancer therapies and discuss the prospects of hyperoxia therapy in cancer treatment.
Thermodynamic 2D Silicene for Sequential and Multistage Bone Regeneration
Authors: Ni Ni, Min Ge, Rui Huang, Dandan Zhang, Han Lin, Yahan Ju, Zhimin Tang, Huiqin Gao, Huifang Zhou, Yu Chen, Ping Gu
Journal: Advanced Healthcare Materials (2023)

Bone healing is a multistage process involving the recruitment of cells, revascularization, and osteogenic differentiation, all of which are modulated in the temporal sequence to maximize cascade bone regeneration. However, insufficient osteoblast cells, poor blood supply, and limited bone induction at the site of critical-sized bone defect broadly impede bone repair. 2D SiO
Outcomes with and without outpatient SARS-CoV-2 treatment for patients with COVID-19 and systemic autoimmune rheumatic diseases: a retrospective cohort study
Authors: Grace Qian, Xiaosong Wang, Naomi J Patel, Yumeko Kawano, Xiaoqing Fu, Claire E Cook, Kathleen M M Vanni, Emily N Kowalski, Emily P Banasiak, Katarina J Bade, Shruthi Srivatsan, Zachary K Williams, Derrick J Todd, Michael E Weinblatt, Zachary S Wallace, Jeffrey A Sparks
Journal: The Lancet Rheumatology (2023)
Adult HIV-1 incidence across 15 high-burden countries in sub-Saharan Africa from 2015 to 2019: a pooled analysis of nationally representative data
Authors: Nora E Rosenberg, Bonnie E Shook-Sa, Mincen Liu, Lynda Stranix-Chibanda, Marcel Yotebieng, Nadia A Sam-Agudu, Michael G Hudgens, Sam J Phiri, Wilbroad Mutale, Linda-Gail Bekker, Sizulu Moyo, Khangelani Zuma, Manhattan E Charurat, Jessica Justman, Benjamin H Chi
Journal: The Lancet HIV (2023)
The effect of granulocyte-colony stimulating factor, decitabine, and busulfan–cyclophosphamide versus busulfan–cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial
Authors: Li Xuan, Min Dai, Erlie Jiang, Yu Wang, Fen Huang, Zhiping Fan, Na Xu, Danian Nie, Xinquan Liang, Hong Chen, Jieyu Ye, Pengcheng Shi, Hui Liu, Hua Jin, Ren Lin, Chenhua Yan, Yu Zhang, Jing Sun, Mingzhe Han, Qifa Liu
Journal: The Lancet Haematology (2023)
Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019
Authors: João M Castaldelli-Maia, Yuan-Pang Wang, Andre R Brunoni, Andre Faro, Rafael A Guimarães, Giancarlo Lucchetti, Miquel Martorell, Rafael S Moreira, Kevin Pacheco-Barrios, Jefferson A B Rodriguez, Leonardo Roever, Diego A S Silva, Marcos R Tovani-Palone, Pascual R Valdez, Ivan R Zimmermann, Garland T Culbreth, Simon I Hay, Christopher J L Murray, Isabela M Bensenor
Journal: The Lancet Psychiatry (2023)
Economic evaluation of combined population-based screening for multiple blindness-causing eye diseases in China: a cost-effectiveness analysis
Authors: Hanruo Liu, Ruyue Li, Yue Zhang, Kaiwen Zhang, Mayinuer Yusufu, Yanting Liu, Dapeng Mou, Xiaoniao Chen, Jiaxin Tian, Huiqi Li, Sujie Fan, Jianjun Tang, Ningli Wang
Journal: The Lancet Global Health (2023)
Can white-light endoscopy or narrow-band imaging avoid biopsy of colorectal endoscopic mucosal resection scars? A multicenter randomized single-blind crossover trial
Authors: Mafalda João, Miguel Areia, Teresa Pinto-Pais, Luís Correia Gomes, Sofia Saraiva, Susana Alves, Luís Elvas, Daniel Brito, Sandra Saraiva, Armando Teixeira-Pinto, Isabel Claro, Mário Dinis-Ribeiro, Ana Teresa Cadime
Journal: Endoscopy (2023)

Abstract Background Current guidelines suggest that routine biopsy of post-endoscopic mucosal resection (EMR) scars can be abandoned, provided that a standardized imaging protocol with virtual chromoendoscopy is used. However, few studies have examined the accuracy of advanced endoscopic imaging, such as narrow-band imaging (NBI) vs. white-light endoscopy (WLE) for prediction of histological recurrence. We aimed to assess whether NBI accuracy is superior to that of WLE and whether one or both techniques can replace biopsies. Methods The study was a multicenter, randomized, pathologist-blind, crossover trial, with consecutive patients undergoing first colonoscopy after EMR of lesions ≥ 20 mm. Computer-generated randomization and opaque envelope concealed allocation. Patients were randomly assigned to scar examination with NBI followed by WLE (NBI + WLE), or WLE followed by NBI (WLE + NBI). Histology was the reference method, with biopsies being performed for all tissues. Results The study included 203 scars (103 in the NBI + WLE group, 100 in the WLE + NBI group). Recurrence was confirmed histologically in 29.6 % of the scars. The diagnostic accuracy of NBI was not statistically different from that of WLE (95 % [95 %CI 92 %–98 %] vs. 94 % [95 %CI 90 %–97 %]; P = 0.48). The negative predictive values (NPVs) were 96 % (95 %CI 93 %–99 %) for NBI and 93 % (95 %CI 89 %–97 %) for WLE (P = 0.06). Conclusions The accuracy of NBI for the diagnosis of recurrence was not superior to that of WLE. Endoscopic assessment of EMR scars with WLE and NBI achieved an NPV that would allow routine biopsy to be avoided in cases of negative optical diagnosis.
Impact of Advanced Hybrid Closed Loop on Youth With High-Risk Type 1 Diabetes Using Multiple Daily Injections
Authors: Alisa Boucsein, Antony S. Watson, Carla M. Frewen, Olivia J. Sanders, Jillian J. Haszard, Shirley D. Jones, Philippa J. Milford-Hughes, Martin I. de Bock, Benjamin J. Wheeler
Journal: Diabetes Care (2023)

OBJECTIVE To evaluate glycemic outcomes in youth (aged 13–25 years) with type 1 diabetes and high-risk glycemic control (HbA1c ≥8.5% [69 mmol/mol]) on multiple daily injection (MDI) therapy after transitioning to advanced hybrid closed loop (AHCL) therapy. RESEARCH DESIGN AND METHODS This prospective, 3-month, single-arm, dual-center study enrolled 20 participants, and all completed the study. RESULTS HbA1c decreased from 10.5 ± 2.1% (91.2 ± 22.8 mmol/mol) at baseline to 7.6 ± 1.1% (59.7 ± 11.9 mmol/mol), and time spent in target range 70–180 mg/dL (3.9–10.0 mmol/L) increased from 27.6 ± 13.2% at baseline to 66.5 ± 9.8% after 3 months of AHCL. Two episodes of diabetic ketoacidosis attributed to infusion set failure occurred. CONCLUSIONS AHCL has the potential to improve suboptimal glycemia in youth with type 1 diabetes previously on MDI therapy.